Epithelial Component Research Articles

Mixed Epithelial and Stromal Tumor Family of Kidney (Adult Cystic Nephroma, Mixed Epithelial and Stromal Tumor): Retrospective Clinicopathological Evaluation.

Tumors belonging to the mixed epithelial stromal tumor family (MESTF) are rare; thus clinicopathological experience about them are limited. Each epithelial and stromal component shows different patterns in these tumors. Clinicopathological features of 11 MESTF cases that were diagnosed between 2000 and 2021 at a single center were evaluated. Ten of the 11 patients were female (F:M = 10:1). The mean age of the females was 47 (31-63) years; the male patient was 45 years old. The mean tumor diameter was 6.7 (3.5-19) cm. All tumors had varying proportions of cystic and solid components. Eight cases were well circumscribed, and the others had distinct but irregular borders. Two of the tumors with irregular borders were bulging into the renal sinus. The epithelial component was dominant in most cases. In the epithelial component, macrocyst, microcyst, and tubules were the most common patterns and the most common types of lining epithelium were flat, cuboidal and hobnail. The stromal component was variable in most cases and included hypocellular (mostly collagenous) and cellular areas. In most cases, the cellular stroma had an ovarian-like appearance. Among the other features observed, hyalinization and dystrophic calcification were common. The positivity for estrogen and progesterone receptor in the stromal component was observed in almost all female cases. MESTF, which has distinctive features, should be considered in the differential diagnosis of cystic kidney tumors.

Microinvasive Oral Squamous Cell Carcinoma Redefined by Using Modified Cajal Trichrome Differential Stain − A Histochemical Study

Introduction: In histopathologic laboratories, hematoxylin and eosin (H and E) staining is the routine and gold standard technique employed for biopsy tissues. But, few differential stains are being used in questionable diagnostic cases of oral squamous cell carcinoma (OSCC) to confirm its final diagnosis. Modified Cajal trichrome stain (CTS) is one such stain which may be employed as an adjunctive supporting aid for arriving at a conclusive diagnosis. To assess epithelial and connective tissue components in normal oral mucosa, oral epithelial dysplasia (OED), and OSCC cases stained with routine H and E and modified CTS. And also to compare and evaluate the efficacy of Modified CTS with that of H and E stain. Materials and Methods: A total of 40 tissue samples, 10 each of normal oral mucosa and OED, 20 cases of OSCC (10 cases each of microinvasive and frank OSCC) were stained with standard H and E and modified CTS simultaneously. Results: Modified CTS showed statistically significant and better results in differentiated terms of parameters such as depth of tumor invasion and differentiation between epithelial and connective tissue components in OSCC cases. Epithelial basement membrane interface and microinvasion are clearly appreciated in challenging cases of early epithelial malignancies such as microinvasive OSCC using this stain. Conclusion: As this stain can easily delineate epithelial structures from various connective tissue components, it may be utilized as an auxiliary diagnostic support along with routine H and E stain for confirmatory diagnosis.

Mesonephric-like Carcinosarcoma of the Uterine Corpus: Clinicopathological, Molecular and Prognostic Characteristics in Comparison With Uterine Mesonephric-like Adenocarcinoma and Conventional Endometrial Carcinosarcoma.

This study aimed to investigate the clinicopathological, prognostic and molecular characteristics of uterine mesonephric-like carcinosarcoma (MLCS). We collected clinical, pathological, and genetic information from 12 MLCS patients, and analyzed their differences from mesonephric-like adenocarcinoma (MLA) and conventional endometrial carcinosarcoma (CECS). The epithelial component was exclusively MLA in all MLCS cases. Metastatic and recurrent tumors consisted predominantly or exclusively of MLA in the majority of MLCS cases. Patients with MLCS and MLA presented with more advanced-stage disease than those with CECS. They also exhibited post-treatment recurrence and lung metastases more frequently than CECS. Disease-free survival rates of MLCS and MLA were shorter than those of CECS. Tumor protein 53 gene mutations were detected in four MLCS cases. The predominance or exclusive presence of MLA in metastatic and recurrent tumors highlights the possibility that MLA may determine the clinical outcomes of patients with MLCS. Further studies are required to provide direct molecular evidence of the monoclonal origin of uterine MLCS.

CERBB-2/Her-2 Neu Overexpression and Prognostic Significance in Uterine Carcinosarcoma.

There is not enough data in the literature regarding Her-2 overexpression in uterine carcinosarcomas or its association with the prognosis. The aim of this study was to determine the Her-2 overexpression rate in uterine carcinosarcoma and to evaluate its relationship with the prognosis. Her-2 protein and gene status were evaluated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively, in hysterectomy specimens from 51 patients with uterine carcinosarcoma. Her-2 protein expression in the epithelial component was negative in 42 patients (score 0 in 33 cases, score (+1) in 9 cases), score (+2) in 7 patients and score (+3) in 2 patients. None of the patients had Her-2 protein expression within the sarcomatous component of the tumors. Her-2 gene was not amplified in epithelial or mesenchymal tumor areas according to the FISH method. There was no difference between the Her-2 overexpression negative and positive groups in terms of disease-free survival (DFS) and overall survival (OS). Her-2 overexpression was significantly higher in tumors of patients diagnosed at 65 years or older (p=0.046). In our study, no relationship could be shown between Her-2 overexpression and prognosis in uterine carcinosarcoma. More comprehensive studies are needed to illustrate the relationship between Her-2 overexpression and carcinosarcoma prognosis.

Establishment of Breast Phyllodes Tumor Cell Lines Preserving the Features of Phyllodes Tumors

Abstract Breast phyllodes tumors (PTs) are biphasic, with epithelial and stromal components. Although the PT incidence is low (approximately 1% of all breast tumors), its clinical outcomes are unpredictable, and malignant PTs often progress rapidly. No effective treatment is currently available, thus resulting a high mortality rate from malignant PTs. PT cell lines must be established to facilitate the study of PTs. Herein, we established six PT cell lines through continuous passage or cell immortalization. We characterized these PT cell lines through in vitro functional assays, malignant PT marker detection and short tandem repeat identification. Benign PT cell lines (SYSH-BPT-01 and SYSH-BPT-02) were transfected with human papillomavirus 16 E6/E7, and two malignant PT cell lines (SYSH-MPT-01 and SYSH-MPT-02) were transfected with Simian virus 40 large T antigen. Two malignant PT cell lines (SYSH-MPT-03 and SYSH-MPT-04) were established through continuous passage. All malignant PT cell lines showed greater proliferation, colony formation, migration, invasion and collagen contraction ability than the benign PT cell lines. Moreover, the expression levels of malignant PT markers (α-smooth muscle actin and fibroblast activation protein) and short tandem repeat identification indicated that each PT cell line was identical to the parental primary cells. We successfully established PT cell lines that preserved the features of primary cells. These cell lines may serve as ideal experimental models for studying the function of breast PTs, thus opening new possibilities for PT drug screening and therapeutic target validation.

Neuroendocrine tumor in a longstanding tailgut cyst: a case report

Background: Retrocecal hamartomas are rare cystic lesions due to the persistence of the tailgut. Sometimes the epithelial or mesenchymal components of the cyst wall undergo neoplastic transformation, and, within them, carcinomas and sarcomas can develop. Case Presentation: We present the case of a multicystic lesion, discovered in a patient with perineal pain, which the imaging investigations have localized in the retrocecal space. The histological evaluation performed on his excisional biopsy demonstrates a retrocecal hamartoma harboring a neuroendocrine neoplasm. Conclusion: Tailgut cysts (TGC) are quite rare, only sometimes symptomatic, and infrequently, they also undergo a malignant transformation; in particular, the literature reviews report a higher frequency of adenocarcinomas. The differential diagnosis between lesions with different prognoses and pathogenesis that can develop in the retrocecal space requires a histological examination, which in some cases, becomes essential if we consider the potential for metastatic and local recurrence of any malignant neoplasm that arose in this site.

Role of Immunohistochemistry in the Differential Diagnosis of Pediatric Renal Tumors: Expression of Cyclin D1, Beta-Catenin , PDGFR-Alpha, and PTEN.

Pediatric renal tumors overlap histomorphologically and may cause misdiagnosis. We aimed to determine the role of immunohistochemical staining of Cyclin D1, PTEN, beta-catenin and PDGFR-alpha on pediatric renal tumors. Thirty-six cases of 8 different tumors were included in the study. Four blocks of paraffin tissue microarray were constructed. Cyclin D1, PTEN, beta-catenin and PDGFR-alpha were used in all cases. Staining intensity and extent were graded. All cases of clear cell sarcoma (CCS) and epithelial components of Wilms tumor (WT) showed immunopositivity for Cyclin D1 but blastemal and stromal components of WT were negative. All cases of CCS and most cases of WT consisting of blastemal and stromal components demonstrated loss of expression with PTEN. Cyclin D1 is not a specific immunohistochemical marker due to its strong and diffuse positivity in CCS cases. It may be useful to differentiate CCS from blastemal and stromal components of WT. Other markers except cyclin D1 do not have a role in the differential diagnosis.

The Demographic Characteristics of Patients with Benign Ovarian Cyst and Histological Pattern in a Tertiary Center in Riyadh, Saudi Arabia

Background: Benign ovarian tumours are a very common clinically encountered condition and rarely become malignant. The outcome is generally good, varying from asymptomatic big cysts to symptomatic ones with different sizes. Objective: To know the demography of patients, the types of cyst, presentation and management options. Thereafter, comparison of data with other national and international studies was done. Results: This retrospective cohort study was carried out in Security Forces Hospital, Riyadh in Saudi Arabia between January 1st, 2015 to January 31st, 2018. There were 67 cases of histologically diagnosed benign ovarian neoplasms in that period. The age range of 20-49 made up 72.1% of cases and a mean of 37 years, with a BMI of 20-36.9 Kg/m². 67.2% of cases were electively admitted and 88% of cases had ovarian cyst more than 5cm in size. The affected side was almost similar being 35.8% on right side and 32.8% on the left, 28.3% were bilateral and 2.99% were paraovarian cysts. 31.3% of patients were single and 10.4% multiparous. A parity of up to 6 constituted 41.8% of cases, 58.2% were managed by laparotomy and 41.8% had laparoscopic approach. 56.7% of cases were of epithelial origin, 17.9% functional cyst and 16.4% were Germ cell tumours. Sex cord variety were seen in 5.96% of cases and a combination of epithelial and stromal components made up 2.98% of cases. During the 2-D ultrasound studies done for all patients, 10.4% did not have concomitant Doppler studies done. Of those that had doppler, 8.9% were abnormal. Blood group O positive was seen in 52.2% of cases and 23.9% were ‘A’ rhesus positive and 11.94% were ‘B’ rhesus positive. 4.48% of cases were pregnant at the time of diagnosis. 13.4% had recurrence of cyst, abdominal pain was the main presentation in 59.7% of cases, palpable mass in 4.48%, 22.4% had previous Cesarean Section. Conclusion: To determine the incidence of histologically diagnosed types of benign ovarian neoplasm in a Tertiary hospital in Central part of Saudi Arabia and compare it with other regional areas, in same country, neighboring countries and international figures.Suggestions on certain aspects that were made includes improvements, and that could possibly be a future recommendation, on diagnosis and prognosis of ovarian neoplasm, such as different combinations of tumour markers (CA125 + HE4), surgical management, recurrence rate and blood groups.

Telocytes: Active Players in the Rainbow Trout (Oncorhynchus mykiss) Intestinal Stem-Cell Niche.

Simple SummaryAquaculture is expanding due to the high demand of fish for human consumption. However, since carnivorous fish are fed using fish-derived proteins and lipids, the sustainability of this food-producing sector is debated. Therefore, feed industries and academia are dedicating their efforts to the search for suitable raw materials and more sustainable alternative feeds that are able to ensure the health of the fish. To properly evaluate the effect of these feed formulations, extensive knowledge of the intestinal morphology and physiology is required. Moreover, the intestine is a dynamic environment in which homeostasis is controlled by highly specialized intestinal stem-cell niches. These defined functional units consist of epithelial stem cells, the supportive mesenchymal cell population, and acellular components. While they have been widely studied in the mouse intestine, this understanding is almost absent in fish species. We have previously characterized the organization of the stem-cell niche in the rainbow trout intestine; here, we expand that knowledge by examining telocytes as active stromal components of the niche. Our results indicate that this cell type is also present in rainbow trout and that it represents a key mediator of intestinal homeostasis by virtue of its active interaction with the stem cells.In order to improve the sustainability of trout farming, it is essential to develop alternatives to fish-based meals that prevent intestinal disorders and support growth performances. Therefore, an accurate knowledge of intestinal morphology and physiology is desirable. We previously described the epithelial component of the intestinal stem-cell (ISC) niche in rainbow trout (Oncorhynchus mykiss), which is one of the most successfully farmed species and a representative model of the salmonids family. This work aims to expand that knowledge by investigating the niche stromal components that contribute to intestinal homeostasis. We analyzed samples belonging to five individuals collected from a local commercial farm. Histological and ultrastructural studies revealed peculiar mesenchymal cells adjacent to the epithelium that generated an intricate mesh spanning from the folds’ base to their apex. Their voluminous nuclei, limited cytoplasm and long cytoplasmic projections characterized them as telocytes (TCs). TEM analysis showed the secretion of extracellular vesicles, suggesting their functional implication in cell-to-cell communication. Furthermore, we evaluated the localization of well-defined mouse TC markers (pdgfrα and foxl1) and their relationship with the epithelial component of the niche. TCs establish a direct connection with ISCs and provide short-range signaling, which also indicates their key role as the mesenchymal component of the stem-cell niche in this species. Interestingly, the TC distribution and gene-expression pattern in rainbow trout closely overlapped with those observed in mice, indicating that they have the same functions in both species. These results substantially improve our understanding of the mechanisms regulating intestinal homeostasis and will enable a more detailed evaluation of innovative feed effects.

STRUCTURE OF EXCRETORY DUCTS OF EXTRAAND INFRAORBITAL GLAND OF LABORATORY RATS

The aim of the study. To find out and compare the structure of the excretory ducts of the extraand infraorbital lacrimal gland of the laboratory rat. Object and methods. Five male laboratory rats were examined by dissecting the lacrimal glands, from which a series of thin paraffin sections were obtained for histological examination. Micropreparations were stained with hematoxylin and eosin and examined under a light microscope. Results. It was found that the tubular-alveolar epithelial components of the extraorbital gland of rats inside the lobe are even denser than in the infraorbital gland, as evidenced by very narrow interstitial fissures. The lacrimal glands of laboratory rats have an individual well-defined connective tissue capsule. Inside and between the lobes there are slit-like interpithelial interstitial spaces, in which we do not detect an accumulation of lipocytes, as occurs in the lacrimal glands of man. In the volume of lobes such as the extraorbital and infraorbital glands, the interpithelial interstitial spaces contain vessels of the hemicrocirculatory tract, mainly capillaries, precapillary arterioles and postcapillary venules. Arterioles and venules are usually visualized outside the lobes in more pronounced interstitial spaces. Conclusions. 1. The epithelial tubular structures of the lacrimal gland of the laboratory rat form a complex-branched system of excretory ducts, in which there are no typical intercalated ducts, which would be the connecting component between the terminal section and the excretory duct system. 2. The absence of intercalated ducts leads to a change in the appearance on histological specimens of tubulo-acinar aggregates of the lacrimal glands of rats in favor of tubuloalveolar assemblages. 3. Among the excretory ducts of the lacrimal glands of the laboratory rat, the following can be distinguished: intra-lobular, lobular and common excretory ducts, through which the secret is produced. The common ducts of the extraand infraorbital lacrimal glands, as a rule, combine to form their common duct.

Modern data on embryogenesis and functional morphology of thymus (Literature review, part I)

In the following article we have provided modern data on main stages of implementation, formation as well as stabilization of functional activity of thymus of the fetus on different stages of fetal development. Thus, we have analyzed specific features of gland’s location in case of children, adolescents and adults. We have described two main stages of the organ’s ontogenesis. In addition, histological features of the fetal thymus implemetation, starting with the 8th week of embryonic development were studied and provided below. The criteria of completion of the gland’s formation on the gestational term of 24 weeks were clearly emphasized. The stages of maturing of lymphocytes as well as appearance of the surface markers of the lymphocytes on them as well as division of the T-cells into subpopulations were described. The role of thymus in the sphere of formation of all types of the organism’s immune defence was explained. We have analyzed an endocrine function of the gland with providing the hormones, hormone-like substances, as well as extracts of the organ, which have their influence onto lymphoid tissue development as well as play their leading role in the hormonal homeostasis of the child’s organism. The morphological features of the main structural components of the gland, as well as their functions in the thymus stabilization were disclosed. The nature of relations between structural components was clearly described. It has been proved also, that in case of full-term fetus, the thymus is a main lymphoid organ, which is structurally and functionally formed for the moment of birth. Moreover, under the conditions of the physiological pregnancy the lymphoid and epithelial components are sufficiently and harmoniously developed, and the thymocytes are differentiated and immunologically mature. Finally, we came up with the conclusion, that the pathology of pregnancy and childbirth can lead to the impaired embryogenesis and fetogenesis of the fetal thymus.

MORPHOLOGICAL CHANGES IN SOFT PALATINE TISSUES STANDING BEHIND OBSTRUCTIVE SLEEP APNEA SYNDROME: GENERAL PATTERN AND ROLE OF HUMAN PAPILLOMA VIRUS

snoring and obstructive sleep apnea syndrome (OSAS) are a serious medical problem, as they lead to a complex of complications from various body systems, disrupt the socio-economic sphere and stigmatize patients. To date, a set of treatments has been developed, the most effective of which are conservative therapy using CPAP and surgical interventions - various modifications of uvulopalatopharyngoplasty. However, only a small number of studies have elucidated soft palate tissue pathology in patients with chronic and OSAS. But understanding the morphological changes is one of the key aspects for the development of treatment tactics. The aim of current study is to justify the choice of surgical intervention in the treatment of snoring and OSAS by description of morphological changes of the soft palate and to estimate the impact of HPV infection on the progression of soft palatine remodeling. The study included soft palatine tissue samples, which were removed during surgery for snoring and OSAS in 15 patients. Histological (H&E) and immunohistochemical techniques (Ki-67, p16, Human Papilloma Virus). All patients were divided in two groups according HPV-positivity: 5 persons in HPV-positive group and 10 persons in HPV-negative group. For indicators were estimated: number of cellular layers (CL), number of intraepithelial lymphocytes (per 100 epitheliocytes) (IEL), number of vessels per x100 field (NV), Ki-67 proliferation index (PI). Results shows in HPV+ group: CL - 24,2 (±2,17); IEL - 37,8 (±20,97), NV - 21 (±8,46); PI - 17,6 (±2,51). In HPV- group: CL - 6 (±4,78); IEL - 3,3 (±1,77); NV - 10,7 (±2,67); PI - 7,3 (±2,71). Mann-Whitney criterion shows statistical significant difference between groups for all mentioned indicators. In conclusion: patients with snoring and obstructive sleep apnea syndrome had hypertrophy of the soft palate structures caused by changes in epithelial and connective tissue components. Subepithelial structures underdo the disorganization of connective tissue components with a violation of the histoarchitectonics of collagen fibers, edema and angiomatosis. Thus, the study revealed a number of irreversible pathological processes of soft palate tissues, which is the basis for the choice of surgical treatment tactics including the resection of excess tissue. At the same time HPV-infection leads to more pronounced changes in the epithelial layer and subepithelial tissue with concomitant inflammation that likely to create a negative background for further treatment of OSA syndrome.

Determination of Risk Factors for DCIS Ductal in-situ Carcinoma of Mammary Gland

Mammary gland is altered gland present in skin whose main function in females is that it acts as a lactating gland while in males it is non-functional. When the sample of tissue of mammary gland is observed under microscope it was found that there are 2 major types of tissues which are present. These tissues are epithelial and stromal tissues. The epithelial component of the breast consists of 2 major parts: terminal duct-lobular unit (TDLU) which performs the main secretory function during lactation, and large duct system which performs the function of collection and drainage of secretions; both are interconnected to each other. During the menstrual age of a female patient there are different number of tissues (connective and adipose) is present in the mammary gland these tissues mainly perform as the support system for the mammary gland. Acini, ducts, and lobule are enclosed in intralobular stroma and is mainly formed of connective tissue(loose) myxomatous stroma and some dispersed lymphocyte. The ductal carcinoma is very serious Pathology of breast which is now a major concern in developed country and to a certain extent in developing countries also. There are many major risk factors which are responsible for the same. Some may be of lifestyle based or of genetic based. The treatment for the disease is now possible with advancement in the medical science.
 Purpose for this review article is: Determine the cause affecting factors influencing factors and pathos physiological background of development of DCIS also to describe the gene involved in alteration of cell to enhance tumorous growth and the treatment therapy involved alongside the disease.

Case Report on Benign Spindle Cell Tumour

Introduction: It's an extremely uncommon cancer. First, the epidermis, soft tissues, and connective tissues are impacted. Breast benign spindle cell lesions include a wide range of tumor-like or malignant fibroblastic and myofibroblastic entities. They should be made up entirely of Spindle cells (pure spindle cell lesions) are defined as lesions with no mixed epithelial component.
 Clinical Finding :
 Most Common Symptoms Of Spindle Cell Sarcoma.
 
 • Bone ache. The most frequent sign of spindle cell sarcoma is bone discomfort. The most often afflicted bones by spindle cell sarcoma are those of the...
 Swelling And Tenderness.
 Reduced Mobility.
 Fatigue And Malaise.
 Lump Or Mass.
 
 Diagnostic Evaluation: HB-6.7, TLC:-16, 200, PLT:-15, 000, MCV:-67.0, SR. BILIRUBIN:-0.7
 Therapeutic Intervention – Tab. Allopuraznol 300mg BD, Inj. Emset:- 1.8mg TDS. Inj. Pantop 12mg BD, Inj. Ceftraxon 20ml NS 1 mg BD.
 Outcome- Spindle cell tumours are uncommon cancers that develop in the peripheral and deep tissues of the body. According to a CT scan, a massive tumour encompassed the whole abdomen and pelvis. According to a CT scan, a massive tumour encompassed the whole abdomen and pelvis.
 Conclusion: The patient is admitted to Acharya vinoba bhave rural hospital sawangi (meghe) wardha, under the USG department, where he will get ongoing medical and nursing care, and his health is currently stable and under monitoring.

Epithelial component and intraepithelial lymphocytes of conjunctiva-associated lymphoid tissue in healthy children.

Conjunctiva-associated lymphoid tissue (CALT) plays a key role in protecting the eye surface by initiating and regulating immune responses. The aim of this study was to investigate in healthy children the proportion of intraepithelial lymphocytes (IELs), the degree of viability and/or apoptosis and cell proliferation in three different topographic areas of the conjunctiva. Superior tarsal, superior bulbar, and inferior tarsal-bulbarfornix conjunctival cells were collected by brush cytology (BC) from 24 healthy paediatric subjects (13 boys and 11 girls, mean age 6±2 years) who were to undergo strabismus correction surgery under general anaesthesia. Subsequently, these cells were analysed phenotypically and functionally by flow cytometry (FC). Flow cytometry analysis showed that not all the cells obtained by BC were of the epithelial lineage, but that there was a population of CD45+ cells (IELs) regularly present in the conjunctiva of healthy children. These IELs were mostly T-lymphocytes (CD3+) and B-lymphocytes (CD19+), with higher levels of T-lymphocytes (CD3+) in the upper areas than in the inferior tarsal-bulbar-fornix, where the highest levels of B-lymphocytes (CD19+) were found. In the apoptosis assay, two groups of cell populations were differentiated by cell size and complexity (cytoplasmic granularity), with more complex cells predominating in the upper areas of the conjunctiva and less complex cells being more abundant in the inferior tarsal-bulbar-fornix. Finally, the proliferative capacity of the conjunctival epithelium was significantly higher in the upper tarsal zone than in the rest of the zones analysed. These results suggest that the epithelial component and the IELs of CALT are also regularly present in the conjunctiva of the healthy child, varying in phenotype, viability and cell proliferation according to the different conjunctival regions analysed, which could lead us to believe that each conjunctival zone plays a different, specific role in the regulation of the immune response at the ocular level.

The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma

ObjectiveTo examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization.MethodsThe internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2.ResultsThe mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages (p = 0.038 and p = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio (p = 0.026), CD4_E (p = 0.010), PD-L1_E (p = 0.013) and PD-L1_S (p = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio (p = 0.043), PD-1_E (p = 0.011), PD-L1_E (p = 0.036) and PD-L1_S (p = 0.028) had a significant association with overall survival.ConclusionSome differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling.

Imaging findings of uterine adenosarcoma with sarcomatous overgrowth: two case reports, emphasizing restricted diffusion on diffusion weighted imaging

BackgroundAdenosarcoma is classified as a mixed epithelial and mesenchymal tumor composed of a benign epithelial component and a malignant stromal component. The stromal component in adenosarcoma is usually low grade, and consequently the prognosis is relatively favorable. While, adenosarcoma with sarcomatous overgrowth (SO) is defined as an adenosarcoma in which the sarcomatous component constitutes more than 25% of the tumor. The stromal component is also high-grade sarcoma showing greater nuclear pleomorphism and mitotic activity, thus, it is associated with worse prognosis. MRI findings of adenosarcoma without SO have been described in previous literatures but the imaging findings in adenosarcoma with SO may be poorly defined. Therefore we present two cases of uterine adenosarcoma with SO.Case presentationPatient 1 was a 76-year-old woman referred to our hospital with complaint of abdominal distension and postmenopausal bleeding. Patient 2 was a 57-year-old woman with complaint of lower abdominal pain and abnormal uterine bleeding. On magnetic resonance imaging (MRI), T2 weighted imaging showed a large, heterogeneous high-intensity mass with hyperintense tiny cysts that expanded the uterine cavity and extended into the cervical canal for both patients. On diffusion-weighted imaging (DWI), both masses appeared as high signal intensity. Patient 2 also had a right ovarian adult granulosa cell tumor that may have contributed to development of the adenosarcoma. Patient 1 recurred with peritoneal sarcomatosis 6 months after surgery and died of the disease. Patient 2 also recurred with a left upper lung metastasis 3 months after surgery.ConclusionsDWI may depict pathological changes produced by SO of adenosarcoma as high signal intensity, even though SO does not seem to change MRI findings of adenosarcoma on other sequences. Therefore, DWI could potentially predict SO in presumptive adenosarcoma on MRI and the patient’s prognosis. It is also important for pathologists to know if SO can arise in adenosarcoma because they need to examine the tumor thoroughly to determine the percentage of SO component in the tumor volume when SO is present.

Rhabdomyosarcoma of the uterus in an adult patient with osteopetrosis: a case report

BackgroundUterine sarcoma accounts for 3–7% of uterine malignant neoplasms. It is more aggressive than epithelial neoplasms, and patients have a poor prognosis. Rhabdomyosarcoma is classified as a heterologous uterine sarcoma. It is the most common soft tissue malignancy in children while rare in adults. In young patients, the majority of genital tract rhabdomyosarcomas occur in vagina; however, the most common site of gynecologic rhabdomyosarcoma is cervix followed by uterine corpus, in adults. Uterine corpus rhabdomyosarcoma is rare in adults. Diagnosis of pure rhabdomyosarcoma in uterus involves widespread and perfect sampling as well as precise histopathological evaluation to uncover any epithelial component.Case presentationHere we report a case of pure rhabdomyosarcoma of uterine corpus in a 60-year-old Iranian postmenopausal female who had osteopetrosis, presenting with 8-month heavy vaginal bleeding and a protruding cervical mass. She is alive on 18-month follow-up after treatment.ConclusionsRhabdomyosarcoma of uterine corpus is rare in adults. Diagnosis of pure rhabdomyosarcoma in uterus involves widespread and perfect sampling as well as precise histopathological evaluation to uncover any epithelial component. Treatment options in adult gynecological rhabdomyosarcoma are based on studies in younger patients, and more studies may help us choose the best approach for improving outcome.

Primary mediastinal germ cell tumours: an immunohistochemical and molecular diagnostic approach.

Primary mediastinal germ cell tumours (PMGCTs) are rare mediastinal neoplasms, and their diagnosis can be challenging, owing to small biopsy samples. The aim of this study was to develop a diagnostic algorithm using immunohistochemical staining, with a focus on novel markers, and molecular analysis of isochromosome 12p [i(12p)]. Paraffin-embedded tissues of 32 mediastinal tumours were analysed with immunohistochemical staining for sal-like transcription factor 4 (SALL4), Lin-28 homologue A (LIN28), octamer-binding transcription factor 3/4 (OCT3/4), D2-40, cluster of differentiation 117 (CD117), sex-determining region Y-box 17, sex-determining region Y-box 2 (SOX2), cluster of differentiation 30, the β-subunit of human chorionic gonadotropin (β-hCG), GATA-binding protein 3 (GATA3), forkhead box protein A2 (FOXA2), glypican-3 (GPC3), α-fetoprotein (AFP), terminal deoxynucleotidyl transferase (TdT), nuclear protein of the testis (NUT), and pan-cytokeratin. Quantitative real-time polymerase chain reaction was performed to investigate the i(12p) status. Fifteen seminomas, seven teratomas, one yolk sac tumour, one choriocarcinoma and seven mixed PMGCTs were diagnosed. Each entity had different immunohistochemical staining patterns, which helped to distinguish them: OCT3/4, D2-40, CD117 and TdT for seminoma; OCT3/4 and SOX2 for embryonal carcinoma; FOXA2, GPC3 and AFP for yolk sac tumour; and β-hCG and GATA3 for choriocarcinoma. Mature teratomas stained positively for pan-cytokeratin in epithelial components and focally for SALL4, SOX2, GATA3, D2-40, and FOXA2. Furthermore, a NUT carcinoma mimicking a PMGCT was diagnosed, showing strong nuclear SOX2 staining and speckled nuclear NUT staining. i(12p) was detected in 24 of 27 PMGCTs (89%). A diagnostic algorithm is of great importance for a reliable diagnosis of PMGCT in, usually small, tissue biopsy samples. Therefore, a combination of three to four antibodies to identify the correct histological subtype is usually necessary, in addition to morphological features. The i(12p) status serves as an additional option to indicate a germ cell origin in selected cases.

Immune-Mediated Reprogramming of Intestinal Stem Cells Drives STAT1-Dependent Myc Expression and Epithelial Regeneration in GI-Gvhd

Crypt apoptosis and regeneration are characteristic findings in GI-GVHD. Intestinal stem cells (ISCs) are critical for maintaining the intestinal epithelium, but their frequencies are reduced in experimental GVHD, and the mechanisms driving crypt regeneration in this context are poorly understood.To better understand the impact of GVHD on individual epithelial components, we performed single cell RNA sequencing (scRNAseq) of purified small intestine crypts from B6 mice during homeostasis and five days after B6 into B6 syngeneic (syn) or B10.Br into B6 allogeneic (allo) BMT. Sequenced cells were first partitioned into distinct clusters using PhenoGraph, and the cluster identities were annotated based on their gene expression profiles. Unsupervised clustering indicated multiple subpopulations within the various recognized crypt components (Fig 1A). While secretory lineages clustered similarly across experimental conditions, there was highly distinct clustering among ISC populations and striking dissimilarity between allo and syn ISCs. Quantification by computing the subpopulation's phenotypic distance, a composite score integrating both the number and amplitude of differentially expressed genes, indicated that ISCs demonstrated the greatest transcriptional change in response to GVHD among all crypt lineages (Fig 1B). Gene Set Enrichment Analysis (GSEA) highlighted activation of the interferon-γ (IFNγ) pathway in allo ISCs, and differential gene expression indicated that STAT1 was their most highly upregulated transcription factor. We then performed MHC-mismatched allo-BMT into STAT1-floxed x villin-Cre recipients. Consistent with a role in IFNγ-related toxicity, STAT1-deficient recipients initially demonstrated reduced GVHD pathology, as well as a reduction in proliferating Ki67 + cells (Fig 2A). However, the pathology reduction in STAT1-deficient recipients was transient, while reduction in crypt proliferation persisted. STAT1-deficient recipients ultimately demonstrated increased mortality after allo-BMT, indicating a complex response to epithelial STAT1 signaling in GVHD.While IFNγ can induce epithelial apoptosis and kill organoid cultures, organoid exposure to IFNγ augmented size even at IFNγ concentrations that did not impair viability in a STAT1-dependent manner, and co-culture with allo T cells augmented organoid size (Fig 2B, C). Moreover, cell cycle analysis showed augmentation of cell cycle in ISCs after IFNγ treatment in association with upregulation of cyclin D1 (Fig 2D), and human organoids also showed increased size in response to IFNγ treatment, further suggesting that this growth promotion was not simply a secondary response to tissue injury.In addition to the IFNγ signaling, GSEA of allo ISCs indicated activation of the Myc pathway. scRNAseq data showed specific upregulation of Myc in allo ISCs (Fig 3A). Myc expression within individual ISCs indicated that greater STAT1 expression and IFNγ signaling directly correlated with Myc expression in the same ISCs, providing a potential direct link between T-cell-derived IFNγ and ISC-dependent regeneration (Fig 3B). Additionally, intestinal organoid qPCR showed that Myc expression was upregulated after IFNγ treatment, and scRNAseq of IFNγ-treated organoids indicated this Myc upregulation was restricted to the ISC/progenitor compartment. Although Myc is downstream of Wnt signaling, which is critical for ISC maintenance, expression of the representative Wnt target gene Axin2 was downregulated after IFNγ treatment, and Irf1, a representative IFNγ/STAT1 target gene, was upregulated, suggesting that IFNγ/STAT1 signaling could replace Wnt/β-catenin as a driver of ISC Myc expression. We next examined Myc function and found that treatment with the Myc inhibitor 10058-F4 suppressed IFNγ-dependent organoid growth (Fig 3C). Finally, immunofluorescent staining showed Myc protein expression in intestinal crypts after allo-BMT in a STAT1-dependent manner (Fig 3D), and Myc inhibitor treatment in vivo suppressed crypt epithelial proliferation in mice with GVHD.In summary, we found that epithelial STAT1 contributes to crypt regeneration in GVHD by transmitting T-cell-derived JAK/STAT cytokine signaling to activate Myc expression in ISCs. Clinical use of JAK inhibitors in GVHD may inhibit this regenerative response, necessitating concurrent interventions aimed at restoring it. [Display omitted] DisclosuresHanash: Evive Biotech: Ended employment in the past 24 months.